Broad Goals: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders that causes infertility in women. Its marked phenotypic variability, puzzling list of potentially associated conditions, and hence potential risk to a women's health over a lifetime remain a clinical investigational challenge. To a great extent, this variability can be attributed to the marked genetic and environmental heterogeneity of the populations studied. We will address many of these long-term obstacles by studying PCOS in Iceland where we can take advantage of the country's relative genetic and environmental homogeneity, the remarkably rich genealogic database, and their centralized healthcare information. There, aggregation of large numbers of PCOS families whose homogeneity reduces genetic variance can be used to map the genetic basis for this condition. Finally, as the genes responsible for PCOS become evident, determining their consequences and phenotype/genotype correlations in Iceland and contrasting them with US women will be possible for the first time. Specific Aim 1 is to determine the intermediary phenotypes of women with PCOS in Iceland and contrast them to US women with PCOS Specific Aim 2 is to combine Iceland's genealogic database that can identify relationships between affected individuals and construct extended pedigrees with high-density, genomewide scans to determine the genetic basis of PCOS. Specific Aim 3 is to contrast the association of loci, at risk haplotypes, and/or mutations in candidate genes in Icelandic women with PCOS to their U.S. counterparts. Specific Aim 4 is to identify the genotype/phenotype correlations between the identified genes and the multiple organ system defects observed in women with PCOS Specific Aim 5 is to use genealogic information to evaluate the long-term health risks associated with PCOS.